Early prophylactic inhaled beclomethasone in infants less than 1250 g for the prevention of chronic lung disease.

OBJECTIVE: Inflammation plays an important role in the development of chronic lung disease (CLD), which has become a major cause of morbidity in surviving infants less than 1250 g at birth. The authors hypothesized that the progression of this inflammation and, therefore, the establishment of CLD would be decreased with the use of early prophylactic inhaled corticosteroids. Short, and long term respiratory and neurodevelopmental outcomes were also examined. DESIGN: A double-blind, randomized placebo controlled trial. SETTING: Level-III neonatal intensive care unit. POPULATION STUDIED: Sixty infants less than 1250 g at birth, diagnosed with respiratory distress syndrome and requiring ventilatory support at 72 h of age were enrolled in the study. INTERVENTION: Infants enrolled received either placebo or beclomethasone diproprionate by a metered dose inhaler, which was used in-line with the ventilator circuit while the infant was ventilated and then via a spacer until 28 days of age. RESULTS: Thirty infants were given beclomethasone and 30 were given placebo. There were two deaths in each group. Among the surviving infants, the frequency of moderate-to-severe CLD was 17% in each study group. Mean time to extubation was not different for beclomethasone compared with placebo at 16.4 and 12.5 days (P=0.12), respectively. The requirement for intravenous corticosteroids was lower in the beclomethasone-treated group (RR 0.67, 95% CI 0.43 to 1.04), although this difference was not statistically significant. The incidence of growth failure, infection and intraventricular hemmorhage did not differ between the two groups. Long term outcomes were not different with respect to the incidence of respiratory re-admissions, cerebral palsy, developmental delay, blindness or deafness. CONCLUSIONS: Early treatment with inhaled beclomethasone diproprionate did not reduce the incidence of CLD or decrease the duration of mechanical ventilation. The decrease in intravenous corticosteroid use was not statistically significant. Long term outcome was not affected.

Massive pericardial effusion as a cause for sudden deterioration of a very low birthweight infant.

We describe the successful resuscitation of a very low birthweight infant after sudden deterioration caused by a massive pericardial effusion. The neonatal course of this 740 gm, 26-week gestational age infant had been complicated by moderate respiratory distress syndrome, apnea, and bronchopulmonary dysplasia. A Silastic catheter was placed percutaneously in the right axillary vein on day 6 of life and documented to be in the superior vena cava prior to continuous parenteral nutrition. On day 38, her cardiorespiratory status abruptly deteriorated, blood return could not be obtained from the central line, and it was removed. Chest radiograph and subsequent echocardiogram confirmed a massive pericardial effusion. Under echocardiographic guidance, an emergency percutaneous pericardiocentesis allowed aspiration of 23 ml of straw-colored fluid. Her vital signs immediately returned to normal and reaccumulation of the effusion did not occur. Despite the high mortality of premature infants from pericardial effusion as a complication of central venous catheterization, early diagnosis and prompt therapy can assure a good outcome. As a cause of sudden deterioration of very low birthweight infants, tamponade must not be forgotten, since it is now a rapidly treatable complication of central venous cannulation.

Effect of high-dose vitamin D supplementation on radiographically detectable bone disease of very low birth weight infants.

To test the hypothesis that high-dose vitamin D2 supplementation would result in a lower incidence of radiographically detectable bone disease, we randomly assigned 40 very low birth weight infants to a control group who received vitamin D2 in a dosage of 400 IU/day and 41 to an experimental group who received a dosage of 2000 IU/day. After 6 weeks, radiographs from all infants were scored blindly for degree of radiographic bone disease, and serum osteocalcin and 25-hydroxyvitamin D levels were measured. Mean vitamin D intake was 360 +/- 141 (SD) IU/day in the control group and 2170 +/- 144 (SD) IU/day in the experimental group. Median 6-week serum 25-hydroxyvitamin D levels were 24 ng/ml (range 3 to 60 ng/ml) in the control group and 68 ng/ml (range 9 to 150 ng/ml) in the experimental group (p less than 0.001). Overall, 20% of the infants had evidence of moderate radiographic bone disease and only 2% were severely affected. The radiographic bone score (median = 2.5) and serum osteocalcin concentration (mean = 21.7 +/- 8.7 ng/ml) in the control subjects did not differ significantly from those in the experimental group (median bone score = 2.0; mean osteocalcin level = 24.1 +/- 7.9 ng/ml). Although there may be a subset of very low birth weight infants who would benefit from high doses of vitamin D, we conclude that no generalized clinical improvement can be attributed to this regimen alone.

Drug errors and incidents in a neonatal intensive care unit. A quality assurance activity.

We prospectively examined the causes of medication errors and incidents in a level 3 neonatal intensive care unit for a 2-year period. There were 313 incidents in 23,307 patient days (13.4 incidents per 1000 patient days). The relative risk of incidents was greater in more intensive levels of care. The two most common causes of incidents were neglecting to give a medication on schedule (n = 52) and nonregulation of an intravenous infusion (n = 32). Twenty percent of orders made by physicians that were in error resulted in serious incidents compared with only 6% of all other causes.

Effect of timing of cerebral ultrasonography on the prediction of later neurodevelopmental outcome in high-risk preterm infants.

To determine the predictive value of cranial ultrasonographic examination in high-risk preterm infants at different postnatal ages, we scanned 110 infants less than or equal to 32 weeks gestational age at 1, 2, 3, and 6 weeks postnatal ages and at 40 weeks postconceptional age (PCA). Cranial abnormalities detected by ultrasonography at each postnatal age of examination were classified as minor (periventricular superolateral echogenicity with or without intraventricular hemorrhage, grades 1 to 3) or major (cystic periventricular leukomalacia with or without intraventricular hemorrhage, grade 4) and correlated with neurodevelopmental outcome determined by 1 year of age. Major abnormalities detected by ultrasonography were present in four infants at 1 week, four at 2 weeks, eight at 3 weeks, and 11 infants at 6 weeks and 40 weeks PCA, respectively. Nineteen infants (17%) had moderate to severe functional handicaps defined as cerebral palsy, cognitive or visual deficit, or deafness. The positive and negative predictive values of ultrasound examinations, with regard to later neurodevelopmental outcome, improved with increasing postnatal age at examination and was best at 40 weeks PCA. Negative results of ultrasound study at 40 weeks PCA most correctly predicted satisfactory outcome. Although only 58% of moderately to severely handicapped infants were correctly identified by ultrasound examination at 40 weeks PCA, all infants with major ultrasonographic abnormalities at 40 weeks PCA had moderate or severe handicap. Our data demonstrate that the timing of cerebral ultrasonography is important in the prediction of later neurodevelopmental outcome in high-risk preterm infants.

Preterm birth at 23 to 26 weeks' gestation: is active obstetric management justified?

To determine if active perinatal management was justified in preterm deliveries at less than or equal to 26 weeks' gestation, the outcome (survival and short- and long-term morbidity) of 43 infants (group I) born between 23 and 26 weeks' gestation was compared with that of 17 infants (group II) born at 27 weeks' gestation. Of the 12 surviving infants in group I (survival 28%), 11 were ventilated (median = 50 days), eight had moderate to severe bronchopulmonary dysplasia, and four had mild retrolental fibroplasia. At follow-up, two infants had physical disabilities with moderate to severe functional impairment, one had a minor disability, and nine had normal neurodevelopment. In contrast, of the 13 surviving infants in group II (survival 76%), nine were ventilated (median = 8 days), six had moderate to severe bronchopulmonary dysplasia, and six had mild RLF. At follow-up, one infant had a physical disability with moderate to severe functional impairment, four had minor disabilities, and eight had normal development. Perinatal factors that positively influenced survival in the two groups combined included active perinatal management, antenatal steroids, female sex, and absence of clinical chorioamnionitis and asphyxia. Although group I infants had a significantly higher mortality rate (p less than 0.05) and required a longer duration of ventilation (p less than 0.05), no differences in the incidence of postnatal complications or long-term morbidity at 2 to 4 years of age were evident between the two groups.

Perinatal listeriosis: report of an outbreak.

From April to August, 1981, 15 cases of perinatal listeriosis were seen in Halifax, Nova Scotia, Canada. Nine of the 15 mothers presented with 'flu-like' symptoms, 3 had symptoms of an upper respiratory infection and 2 a history of fever alone. During labor 11 mothers had fevers greater than 38 degrees C and 9 had stained amniotic fluid. Twelve delivered prematurely. Among the 15 infants the most common clinical features were perinatal depression, respiratory distress, fever, hematologic abnormalities and rash. There were 7 deaths (case fatality rate of 46.7%). A transplacental route of infection for the fetus was suggested by the signs of systemic illness in most mothers, the lack of positive maternal vaginal cultures and evidence of chorioamnionitis, premature labor, severe fetal disease and intrauterine death prior to membrane rupture. The delivery of healthy infants to two mothers who had received antepartum treatment for listeriosis suggests that earlier recognition and treatment of maternal disease will improve perinatal outcome.

Follow-up study of survivors of fetal and early onset neonatal listeriosis.

Although fetal or neonatal infection with Listeria monocytogenes is known to have a high mortality, the longterm morbidity is unknown. Clinical sequelae of fetal or neonatal listeriosis were studied in eight survivors of such infections at a mean age of 16 months corrected for prematurity. A developmental and health history was taken and a Denver Developmental Screening Test and neurological exam performed on each subject. Two infants were seen again and the remainder had developmental and health histories obtained from their mothers and primary physicians at a mean age of 31 months. Six of the eight infants studied had no evidence of neurodevelopmental sequelae. Four of these six had mild or no clinical disease after birth. However, two of the six intact survivors, both born prematurely, were critically ill in the early postnatal period. The two remaining infants had neurodevelopmental handicap. In addition to being prematurely born with severe perinatal disease, these two had CNS complications in the newborn period, both with meningitis and one with intraventricular hemorrhage. Although intelligence in both appeared to be normal, one had mild and the other moderate spastic diplegia. Severe perinatal disease, including fetal or neonatal death, appeared to be related to delayed or no antepartum antibiotic therapy of mothers. Premature delivery appeared to be an important factor both in the severity of disease and in the development of longterm handicap. There were no deaths and no longterm sequelae in infants born at a gestational age greater than 37 weeks. However, in the absence of meningitis and other CNS complications, it would appear that the prognosis even for prematurely born survivors of perinatal listeriosis is very good.

Progressive hydrocephalus in infants with birth weights less than 1,500 g.

Premature infants have been frequently observed to manifest hydrocephalus after intraventricular hemorrhage (IVH). For the complete newborn population of Nova Scotia in 1976 to 1978, we found a very low incidence of hydrocephalus in children whose birth weight was less than 1,500 g. Eighty-two percent of these babies were born in a perinatal center; 18% were transported. Chart review of survivors (58%) and autopsy review of deaths (autopsy rate, 86%) showed that in the province's three neonatal intensive care units, only four of 314 such babies manifested progressive hydrocephalus. Only one of four infants was examined after IVH. An IVH was noted at autopsy in 42% of cases. No survivor manifested hydrocephalus one to three years later as judged by head circumference and neurosurgical records. Our results may reflect the impact of regionalized perinatal care, or that post-IVH hydrocephalus is rare in an unselected population.

Hypercapnia and right-duct lymph flow in pups and adult dogs.

The effect of moderate hypercapnia on right-thoracic duct lymph flow, pulmonary hemodynamics, and lung water content was studied in seven 2- to 5-wk-old dogs and eleven adult dogs anesthetized with pentobarbital, paralyzed with succinylcholine, and maintained on intermittent positive-pressure ventilation. Following a 30-min control period in which arterial pH and blood gases were maintained within normal limits, the dogs were ventilated with 3-14% CO2 for 30 min; they were then returned to control conditions fro a 30-min recovery period. Hypercapnia was associated with a significant increase in lymph flow rate in both pups and adult dogs (P less than 0.05) and a significant increase in pulmonary artery and pulmonary artery wedge pressures in adult dogs (P less than 0.05). These data suggest that hypercapnia may increase the net flow of water out of the pulmonary vascular bed.

Serum triiodothyronine and thyroxine in the neonate and the acute increases in these hormones following delivery.

Low triiodothyronine (T(3)) and high normal thyroxine (T(4)) concentrations are present in cord sera from full term infants. To examine this phenomenon further, radioimmunoassay of T(3) and T(4) was carried out in paired maternal and cord sera as well as capillary sera from neonates at different intervals after delivery. Free T(3) and free T(4) concentrations were also estiamted in cord and maternal sera by equilibrium dialysis. In 12 paired specimens, the T(3) concentration in cord sera was significantly lower than the maternal level (51+/-4 vs. 161+/-11 ng/100 ml, mean +/-SE). Mean free T(3) concentration was also lower in the cord samples (0.15+/-0.02 vs. 0.31+/-0.04 ng/100 ml). whereas total and free T(4) concentrations were not significantly different. Umbilical vein and artery samples from 11 neonates did not differ significantly in their T(3) and T(4) concentrations. In seven infants the mean T(3) concentration increased from 51+/-3 ng/100 ml at delivery to 79+/-13 at 15 min and 191+/-16 at 90 min. In four other infants the mean T(3) concentration at 24 and 48 h was not significantly different from the 90 min value of the previous group. Less pronounced changes were observed for T(4) which increased from 12.3+/-2.0 mug/100 ml (mean +/-SE) at delivery to 14.1+/-1.9 at 90 min and appeared to have reached a plateau at approximately twice the cord value by 24-48 h after delivery.The maternal-fetal gradient observed for free T(3) is further evidence of the autonomy of the fetal thyroidpituitary axis. The time course of the abrupt increase in serum T(3) in the neonate suggests that it results from the earlier acute increase in serum TSH which occurs shortly after birth. This suggests that the neonatal thyroid contains significant quantities of T(3). Therefore, unavailability of thyroidal T(3) does not appear to explain the low total and free T(3) concentrations present in the sera of newborns.